Project
Innovations for vaccines against helminth infections - WORMVACS2.0
Our ambition is to establish an effective pipeline to support helminth vaccine development and ultimately the control and elimination of some of the world’s most devastating and persistent Neglected Tropical Diseases (NTDs). We aim to achieve this through the development of new vaccines. These vaccines will be based on the results of controlled human infections and animal models, improved target discovery methodology and immunological profiling.The proposed project will have an immediate application in vaccine development for schistosome and hookworm infections, the most important of the helminth infections in terms of detrimental effects on global human health.
Background
Infections with parasitic worms (helminths) continue to cause a massive global health burden. Yet, effective vaccines to enable control and elimination of helminth infections do not exist. Primary reasons for this are 1) target discovery approaches are not well-developed, 2) protective immune mechanisms are only partially clarified at best, 3) production platforms tailored to specific helminth vaccine requirements are not available, and 4) a pipeline for selecting and rapidly progressing pre-clinical and clinical vaccine candidates is generally lacking. Moreover, controlled human infection models are only now being developed and optimized for some of the most important human helminths. These models have not yet been widely implemented in vaccine development programs to date.
Project description
Our task is to provide novel and protective vaccine formulations against and based on newly discovered antigens that will emerge from this project. Existing vaccine candidates in their native form are often glycoproteins, and expectations are that many new candidates will be glycosylated as well. Vaccine candidates in their native form have glycans that either have reported immunomodulatory activities (e.g. directing specific immune responses and promoting specific receptor-mediated pathways of antigen uptake and processing) or that are direct targets of a (protective) antibody response. The plant-based expression platform for secreted helminth glycoproteins (under development at our laboratory) offers a highly versatile and flexible platform, where glycans can be engineered in a modular fashion by co-expressing different glycosyltransferases and/or glycosidases alongside the vaccine candidates. This platform is highly suitable for the production of secreted helminth glycoproteins with a defined glycan composition because: (i) plants are highly tolerant to adaptations in their glycosylation machinery, and (ii) secreted glycoproteins can be produced with a homogenous glycan composition.